Abstract
INTRODUCTION: Two 52-week Phase III studies evaluated the efficacy and safety of once-daily combinations of empagliflozin/linagliptin as monotherapy or add-on to metformin in patients with type 2 diabetes (T2DM). The aim of this analysis was to further assess the safety and tolerability of empagliflozin/linagliptin compared with their individual components in patients with T2DM, using pooled data from these trials. METHODS: A total of 1363 patients were treated with empagliflozin 25 mg/linagliptin 5 mg (n = 273), empagliflozin 10 mg/linagliptin 5 mg (n = 272), empagliflozin 25 mg (n = 276), empagliflozin 10 mg (n = 275), or linagliptin 5 mg (n = 267). Adverse events (AEs) were assessed descriptively in patients who took ≥ 1 dose of study drug. RESULTS: Total exposure was 251, 255, 256, 249, and 243 patient-years in the empagliflozin 25 mg/linagliptin 5 mg, empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg, and linagliptin 5 mg groups, respectively. The proportion of patients with ≥ 1 AE was similar across groups (70.4-74.9%). The percentage of patients with confirmed hypoglycemic AEs (plasma glucose ≤ 70 mg/dL and/or requiring assistance) was low in all groups (1.1-2.2%); none required assistance. Events consistent with urinary tract infection were reported in similar percentages of patients in all groups (11.4-13.8%), and in a greater proportion of female than male patients. Events consistent with genital infection were reported in higher percentages of patients on empagliflozin/linagliptin or empagliflozin (4.0-6.5%) than linagliptin 5 mg (2.6%), and in a greater proportion of females than males. The risks of hypersensitivity reactions and events consistent with volume depletion were low across treatment groups. CONCLUSION: Empagliflozin/linagliptin as monotherapy or add-on to metformin for 52 weeks was well tolerated in patients with T2DM, with safety profiles similar to individual components, including a low risk of hypoglycemia. FUNDING: The Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT01422876 & NCT01422876.